| Abstract |
The virulence of Vibrio parahaemolyticus, a seafood-borne pathogen, is mediated by an array of factors, including type III and type VI secretion systems (T3SS and T6SS) and thermostable direct hemolysin (TDH). The GntR-family transcriptional regulator SbfR (VP1649) has recently been identified as a repressor of biofilm formation and an activator of motility. However, its role in regulating the pathogen's virulence remains unexplored. This study demonstrates that SbfR is a pivotal regulator of key virulence phenotypes in V. parahaemolyticus. Deletion of sbfR significantly attenuated lethality in a zebrafish infection model. The mutant exhibited enhanced adhesion to HeLa cells but caused significantly less cytotoxicity. Hemolytic activity, as determined by the Kanagawa phenomenon (KP) test, was unaffected. At the molecular level, SbfR acted as a transcriptional repressor of genes associated with T6SS2 (hcp2, VPA1043, VPA1044) and the Vp-PAI master regulator vtrA, while it activated the expression of T3SS1-related genes (exsA, VP1667, VP1687). Two-plasmid lacZ reporter assays in a heterologous E. coli system confirmed that SbfR may directly modulate the promoter activities of these T6SS2 and T3SS1 genes. Our findings establish SbfR as a transcriptional regulator that represses adhesion mediated by T6SS2, promotes T3SS1-dependent cytotoxicity, and is essential for full pathogenicity in vivo.
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